Diltiazem prolonged effects of alfentanil in one study
Clinical evidence,mechanism, importance and management
A 24 % increase in AUC of alfentanil and a 50 % increase in its half-life were seen in 15 patients anaesthetised with midazolam and alfentanil (induced with 50 micrograms/kg, then maintained with 1 microgram/kg per minute) when they were given diltiazem 60mg orally 2 hrs before induction, then an infusion for 23 hrs starting at induction. Tracheal extubation was performed on average 2.5 hrs later in patients receiving diltiazem than in a placebo group (See reference number 3). Diltiazem is an inhibitor of cytochrome P450 isoenzyme CYP3A4, which is responsible for metabolism of alfentanil (See reference number 3). Caution is required as there could be an increased risk of prolonged or delayed respiratory depression. The manufacturer says that concurrent use of diltiazem and alfentanil requires special patient care and observation; it may be necessary to lower dose of alfentanil (See reference number 4).
A double-blind, placebo-controlled study in 26 patients undergoing surgery found that 2 doses of slow-release nifedipine 20mg given on day preceding surgery and a further dose given 60 to 90 minutes before surgery increased analgesic effect of morphine (See reference number 5). A study in animals found that verapamil potentiated morphine analgesia (See reference number 6). A further study in animals found that diltiazem, nimodipine and verapamil, given before morphine, potentiated analgesic effect of morphine and markedly increased morphine serum levels (See reference number 7).
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